Ivosidenib

On July 20, 2018, Ivosidenib (trade name: Tibsovo) was approved by the FDA for use in the treatment of adult patients with recurrent or refractory acute myeloid leukemia (AML) with IDH1 mutations.

The original manufacturer of Ivosidenib is Agios Pharmaceuticals.

Ivosidenib can target the IDH1 metabolic pathway, inhibit the activity of mutated IDH1 enzymes, and prevent the accumulation of metabolite 2-HG, thereby playing an anti-cancer role.

1.Main components

Ivosidenib

2.Adapt to the population

Ivosidenib is suitable for acute myeloid leukemia and Carcinoma of bile duct.

3.Medication for special populations

3.1Pregnancy

Based on animal embryo-fetal toxicity studies, Ivosidenib may cause fetal harm when administered to a pregnant woman. There are no available data on Ivosidenib use in pregnant  women to inform a drug-associated risk of major birth defects and miscarriage. In animal embryo-fetal toxicity studies, oral administration of ivosidenib to pregnant rats and rabbits  during organogenesis was associated with embryo-fetal mortality and alterations to growth starting at 2 times the steady state clinical exposure based on the AUC at the recommended human dose. If this drug is used during pregnancy, or if the patient becomes pregnant  while taking this drug, advise the patient of the potential risk to a fetus.

3.2Lactation

There are no data on the presence of ivosidenib or its metabolites in human milk, the effects on  the breastfed child, or the effects on milk production. Because many drugs are excreted in human  milk and because of the potential for adverse reactions in breastfed children, advise women not  to breastfeed during treatment with Ivosidenib and for 1 month after the last dose.

3.3Pediatric Use

The safety and effectiveness of Ivosidenib in pediatric patients have not been established.

3.4Geriatric Use

Of the 304 patients who received Ivosidenib in the clinical studies for AML and MDS, 75%  were 65 years of age or older and 35% were 75 years or older.  Of the 124 patients with cholangiocarcinoma treated with Ivosidenib in Study AG120-C-005,  37% were 65 years of age or older and 11% were 75 years or older.  No overall differences in effectiveness or safety were observed between patients who were 65 years and older compared to younger patients.

3.5Renal Impairment

No modification of the starting dose is recommended for patients with mild or moderate renal  impairment (eGFR ≥ 30 mL/min/1.73m2 , MDRD). The pharmacokinetics and safety of  ivosidenib in patients with severe renal impairment (eGFR < 30 mL/min/1.73m2 , MDRD) or  renal impairment requiring dialysis are unknown. For  patients with pre-existing severe renal impairment or who are requiring dialysis, consider the  risks and potential benefits before initiating treatment with Ivosidenib.

3.6Hepatic Impairment

No modification of the starting dose is recommended for patients with mild or moderate (Child-Pugh A or B) hepatic impairment. The pharmacokinetics and  safety of ivosidenib in patients with severe hepatic impairment (Child-Pugh C) are unknown. For  patients with pre-existing severe hepatic impairment, consider the risks and potential benefits  before initiating treatment with Ivosidenib.

4.Drug overdose

Drug overdose is not yet clear.

5.Drug storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F).

6.Pharmacokinetics

The AUC and Cmax of ivosidenib increase in a less than dose-proportional manner from  200 mg to 1,200 mg daily (0.4 to 2.4 times the approved recommended dosage). The  following ivosidenib pharmacokinetic parameters were observed following  administration of ivosidenib 500 mg as a single dose or daily dose (for steady state),  unless otherwise specified. The steady-state pharmacokinetics of ivosidenib 500 mg  were comparable between patients with newly diagnosed AML, relapsed or refractory  AML, and relapsed or refractory MDS, and were lower in patients with cholangiocarcinoma.

from FDA，2023.10